This is a revised application for a K23-Mentored Patient-Oriented Career Development Award. It includes evidence of substantial progress in the career development of Dr. Elkins and new preliminary data to support the research plan. The overall goal of this proposal is to provide structured mentoring, didactics and research that will prepare Dr. Elkins for a career as an independent investigator in the field of vascular cognitive impairment. The program will provide advanced training in the genetic and epidemiological study of disease susceptibility. Dr. Elkins is trained as a specialist in neurovascular disease and has a proven record of research success with his mentors, who are each recognized leaders in their respective fields. High performance on cognitive tests is increasingly rare as people age. Individuals who maintain high cognitive function may have less exposure to risk factors for dementia. Our preliminary data indicates that they may also be less susceptible to their effects on cognition. We propose to study a cohort of 2000 non-demented elderly, age 80 years and older, who have been followed in a managed care organization over the last 30 to 40 years. Our primary hypothesis is that high cognitive function is associated with both less exposure to hypertension and less susceptibility to end-organ injury from hypertension. We propose the following Specific Aims: 1) Determine if there is an independent relationship between high cognitive function and life-time exposure to hypertension, 2) determine if individuals with high cognitive function are less susceptible than others to developing cardiovascular complications of hypertension, 3) determine if ACE haplotype or the D/I polymorphism modifies the relationship between exposure to hypertension and cognitive function. This long-term goal is to identify factors that protect the brain from vascular injury and to foster Dr. Elkins's development as an independent researcher into the genetic and clinical determinants of susceptibility to complex human diseases.